Effect of epidermal polyamine depletion on the accumulation of methylglyoxal bis(guanylhydrazone) in mouse skin.
A systemic or topical treatment of mice with alpha-difluoromethylornithine, and irreversible inhibitor of mammalian ornithine decarboxylase, produced a rapid depletion of epidermal putrescine and spermidine. When methylglyoxal bis(guanylhydrazone), another inhibitor of polyamine biosynthesis and a potent antiproliferative agent, was subsequently administered the epidermal concentration of the latter drug rose distinctly higher than without a prior difluoromethyl ornithine treatment. The combined use of these 2 antimetabolites of polyamines also profoundly depressed epidermal DNA synthesis, especially in UV-irradiated skin. A "priming" with difluoromethyl ornithine may therefore offer a means to enhance the epidermal accumulation of otherwise poorly absorbed methylglyoxal bis(guanylhydrazone).
D000818:Animals; D000518:Eflornithine; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008935:Mitoguazone / Q000032:analysis / Q000494:pharmacology*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D011073:Polyamines / Q000037:antagonists & inhibitors*; D011700:Putrescine / Q000037:antagonists & inhibitors; D012867:Skin / Q000032:analysis / Q000187:drug effects*; D012879:Skin Physiological Phenomena; D013095:Spermidine / Q000037:antagonists & inhibitors
D006146:Guanidines; D011073:Polyamines; D009952:Ornithine; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine